Z. Kevin Lu

Regulatory and clinical considerations for biosimilar oncology drugs

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

Differences in proxy-reported and patient-reported outcomes: assessing health and functional status among medicare beneficiaries

BackgroundProxy responses are very common when surveys are conducted among the elderly or disabled population. Outcomes reported by proxy may be systematically different from those obtained from patients directly. The objective of the study is to examine the presence, direction, and magnitude of possible differences between proxy-reported and patient-reported outcomes in health and functional status measures among Medicare beneficiaries.MethodsThis study is a pooled cross-sectional study of a nationally representative sample of community-dwelling Medicare beneficiaries from 2006 to 2011. Survey respondents can respond to the Medicare Current Beneficiary Survey either by themselves or via proxies. Health and functional status was assessed across five domains: physical, affective, cognitive, social, and sensory status. Propensity score matching was used to get matched pairs of patient-reports and proxy-reports.ResultsAfter applying the propensity score matching, the study identified 7,780 person-years of patient-reports paired with 7,780 person-years of proxy-reports. Except for the sensory limitation, differences between proxy-reported and patient-reported outcomes were present in physical, affective, cognitive, and social limitations. Compared to patient-reports, a question regarding survey respondents’ difficulties in managing money was associated with the largest proxy response bias (relative risk, RR = 3.83). With few exceptions, the presence, direction, and magnitude of differences between proxy-reported and patient-reported outcomes did not vary much in the subgroup analysis.ConclusionsWhen there is a difference between proxy-reported and patient-reported outcomes, proxies tended to report more health and functional limitations among the elderly and disabled population. The extent of proxy response bias depended on the domain being tested and the nature of the question being asked. Researchers should accept proxy reports for sensory status and objective, observable, or easy questions. For physical, affective, cognitive, or social status and private, unobservable, or complex questions, proxy-reported outcomes should be used with caution when patient-reported outcomes are not available.

The role of cerebrovascular disease and the association between diabetes mellitus and dementia among aged medicare beneficiaries

The aim of this study is to assess whether diabetes mellitus is associated with overall dementia and its subtypes (Alzheimers disease and vascular dementia) among the elderly and to identify the role of cerebrovascular disease in the association between diabetes and dementia.

Adherence among Rural HIV-Infected Patients in the Deep South: A Comparison between Single-Tablet and Multi-Tablet Once-Daily Regimens

Background: Once-daily (QD), combination antiretroviral therapy (ART) can impact the willingness and ability of patients to take medications as directed. The impact of antiretroviral (ARV) drug adherence influenced by single-tablet (STR) versus multi-tablet regimens (MTR) among patients enrolled in the AIDS Drug Assistance Program (ADAP) in a rural environment has not yet been assessed. Material and Methods: A retrospective chart review evaluated adherence and outcomes in adult HIV-infected patients enrolled in the ADAP at 2 ambulatory clinics in the Southeast, taking either a QD STR (efavirenz [EFV]/emtricitabine/tenofovir [TDF]) or a QD protease inhibitor (PI)-based, MTR (atazanavir [ATV], ritonavir [RTV], and emtricitabine/TDF) by evaluating pharmacy refill records, patient self-reported adherence, and virologic response. Results: A total of 389 patient records were analyzed (STR, n = 165 versus MTR, n = 224). There were more males, a higher percentage of treatment-naive patients, and more patients with a baseline CD4 count of >200 cells/mm3 in the MTR group. Based on refill records, more patients on MTR were >90% adherent (61.6% versus 51.5%, P = .047). In a multivariable analysis, being treatment experienced was a negative predictor (odds ratio [OR] = 0.48, 0.29-0.78) for adherence. Regimen choice was not associated with adherence. More patients taking MTR were virologically suppressed at the end of the observation period. Regardless of the regimen, being >90% adherent was a significant predictor of virologic suppression (OR = 3.51, 1.98-6.23). Conclusion: Treatment-experienced patients enrolled in ADAP are less likely to be adherent. A QD PI-based MTR may result in comparable adherence to an STR in a rural HIV-infected population.

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

ABSTRACT Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and presence of myalgias or muscle complaints, was collected. Myalgias were noted in 3/49 (6.1%) patients receiving combination therapy compared with 5/171 (2.9%) of patients receiving daptomycin alone (P = 0.38). CPK elevations of >1,000 U/liter occurred in 5/49 (10.2%) patients receiving combination therapy compared to 9/171 (5.3%) patients receiving daptomycin alone (P = 0.32). Two of five patients experiencing CPK elevations of >1,000 U/liter in the combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (P = 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population.

Pharmacists’ Familiarity with and Institutional Utilization of Rapid Diagnostic Technologies for Antimicrobial Stewardship

Rapid diagnostic technologies (RDTs) significantly reduce organism identification time and can augment antimicrobial stewardship program (ASP) activities. An electronic survey quantified familiarity with and utilization of RDTs by clinical pharmacists participating in ASPs. Familiarity was highest with polymerase chain reaction (PCR). Formal infectious diseases training was the only significant factor influencing RDT familiarity. Infect Control Hosp Epidemiol 2017;38:863-866.

Hepatitis B virus seroconversion rates among health sciences students in the southeastern United States.

ABSTRACT Objective: To investigate the hepatitis B virus (HBV) seroconversion rate among health sciences students. Participants: The study included pharmacy, doctor of nursing, and medical students over 18 years of age enrolled at the University of South Carolina between 2007 and 2011. Methods: The primary end point was HBV seroconversion rates among students at the initial reporting period. Seroconversion was defined as hepatitis B surface antibody (anti-HBs) level greater than or equal to 10 mIU/mL. Multivariate regression analysis was used to determine predictive factors of seroconversion. Results: Of 777 records, data were available for 709 students. An 83.9% seroconversion rate was observed after a mean of 10 years between vaccine receipt and anti-HBs evaluation. Students with incomplete HBV vaccine series and longer time between initial series and evaluation were less likely to exhibit antibody response. Conclusions: These data highlight the importance of assessment and documentation of HBV vaccination series among health sciences students prior to direct patient care activities.

The impact of dementia on antidiabetic drug use in Medicare beneficiaries with diabetes: findings post-Medicare part D

AIM The objectives of the study were to measure the utilization rates of antidiabetic drugs in diabetic patients with dementia and to assess the impact of dementia on antidiabetic drug use. MATERIALS & METHODS This study was a pooled cross-sectional study of the Medicare Current Beneficiaries Survey from 2006 to 2010. RESULTS & CONCLUSION Lower utilizations of biguanides, DPP-4 inhibitors and thiazolidinediones were observed in dementia patients. The likelihood of using antidiabetic drugs was about 30% (odds ratio: 0.69; 95% CI: 0.56-0.84) lower in dementia patients and 40% (odds ratio: 0.61; 95% CI: 0.44-0.84) lower in patients with Alzheimers disease. Healthcare providers should be aware of underuse of antidiabetic drugs in patients with dementia.